Stringer K A, Bose S K, McCord J M
Department of Pharmacy Practice, School of Pharmacy, Denver, CO 80262, USA.
Free Radic Biol Med. 1997;22(6):985-8. doi: 10.1016/s0891-5849(96)00484-4.
Exogenous plasminogen activators (PAs), such as streptokinase (SK) and tissue plasminogen activator (tPA), have been shown to significantly improve the mortality of patients with acute myocardial infarction. However, reperfusion of the myocardium is associated with neutrophil activation and infiltration into the infarct region. Plasminogen activators influence neutrophil function in vitro, but no data exists regarding the effect of exogenous PAs on inflammation in vivo. Therefore, we evaluated the effect of PAs on inflammation using the carrageenan-induced rat footpad inflammation model. The magnitude of carrageenan-induced inflammation was determined by water-displacement and neutrophil infiltration, following administration of either tPA or SK to Sprague-Dawley rats. tPA (12 mg/kg) inhibited carrageenan-induced inflammation (p < .01). In contrast, administration of SK (40,000 U/kg) enhanced inflammation. These results suggest that exogenous PAs influence the inflammatory process but specific PAs differ in their actions. Ultimately, these differences may influence the efficacy of these agents in the management of acute myocardial infarction and lead to further evaluation of tPA in other inflammatory diseases such as acute respiratory distress syndrome (ARDS) and rheumatoid arthritis (RA), in which neutrophil-mediated injury is likely.
外源性纤溶酶原激活剂（PAs），如链激酶（SK）和组织型纤溶酶原激活剂（tPA），已被证明可显著改善急性心肌梗死患者的死亡率。然而，心肌再灌注与中性粒细胞激活及浸润至梗死区域有关。纤溶酶原激活剂在体外会影响中性粒细胞功能，但关于外源性PAs对体内炎症影响的数据尚不存在。因此，我们使用角叉菜胶诱导的大鼠足垫炎症模型评估了PAs对炎症的影响。在给斯普拉格-道利大鼠注射tPA或SK后，通过排水法和中性粒细胞浸润来确定角叉菜胶诱导的炎症程度。tPA（12毫克/千克）可抑制角叉菜胶诱导的炎症（p <.01）。相比之下，注射SK（40,000单位/千克）会加剧炎症。这些结果表明，外源性PAs会影响炎症过程，但特定的PAs作用有所不同。最终，这些差异可能会影响这些药物在急性心肌梗死治疗中的疗效，并促使对tPA在其他可能存在中性粒细胞介导损伤的炎症性疾病，如急性呼吸窘迫综合征（ARDS）和类风湿关节炎（RA）中的进一步评估。
